Results from a head-to-head phase III trial comparing FCR against a more targeted ibrutinib-based therapy reveal that patients receiving the ibrutinib plus rituximab therapy had a two-thirds reduction in the risk of disease progression relative to those getting standard care. Overall survival was also significantly improved for patients receiving ibrutinib therapy based on current follow-up.
The trial enrolled 529 patients with previously untreated, symptomatic CLL. Participants ranged in age from 28 to 70 (median age 57). Two-thirds of patients received ibrutinib plus rituximab and one-third received a six-month course of FCR. Patient outcomes were tracked for a median of 33,4 months at the time of the analysis.
Rates of survival without disease progression were significantly better in patients who received ibrutinib plus rituximab compared with FCR. In addition, the ibrutinib therapy conferred better overall survival. In subgroup analyses for progression-free survival, ibrutinib was superior to FCR independent of age, sex, performance status and disease stage.
The ibrutinib-treated patients also experienced fewer side effects. Grade 3 and 4 treatment-related adverse events were observed in 58% of the ibrutinib group and 72% of the FCR-treated patients. FCR was more frequently associated with grade 3 and 4 neutropenia (44% vs 23% of the ibrutinib group) and infectious complications (17,7% vs. 7% of the ibrutinib group).
Researchers will continue to monitor patients to determine the durability of these results and how they evolve over time.
„We know FCR does some collateral damage to the immune system that can be long-lasting and leave patients vulnerable to infections, whereas ibrutinib can enhance immune function,‟ said lead author Tait D. Shanafelt, MD, of the Stanford University School of Medicine.
Shanafelt TD et al.: A randomized phase III study of ibrutinib (PCI-32765)-based therapy vs. standard fludarabine, cyclophosphamide, and rituximab (FCR) chemoimmunotherapy in untreated younger patients with chronic lymphocytic leukemia (CLL): a trial of the ECOG-ACRIN Cancer Research Group. ASH Annual Meeting 2018, abstract #LBA4